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Archivos Argentinos de Pediatria Apr 2020Among congenital malformations, heart defects are the most common type of anomaly, and these are associated with a high perinatal, longterm morbidity and mortality. The... (Review)
Review
Among congenital malformations, heart defects are the most common type of anomaly, and these are associated with a high perinatal, longterm morbidity and mortality. The objective of this update was to review the rate of prenatal detection, screening characteristics throughout the pregnancy, in both the first and second trimesters, indications for advanced echocardiography, and to establish a management algorithm in case of prenatal diagnosis of a congenital heart disease. Potential invasive and non-invasive tests and obstetric follow-up will be discussed here. Finally, the main characteristics of fetal therapy in heart anomalies will be reviewed, both cardiac interventions and intrauterine treatment of arrhythmias.
Topics: Female; Fetal Therapies; Heart Defects, Congenital; Humans; Pregnancy; Prenatal Diagnosis
PubMed: 32199055
DOI: 10.5546/aap.2020.eng.e149 -
Archivos Argentinos de Pediatria Jun 2021A seminal study titled Management of Myelomeningocele Study, from 2011, demonstrated that prenatal myelomeningocele defect repaired before 26 weeks of gestation improved... (Review)
Review
A seminal study titled Management of Myelomeningocele Study, from 2011, demonstrated that prenatal myelomeningocele defect repaired before 26 weeks of gestation improved neurological outcomes; based on this study, fetal surgery was introduced as a standard of care alternative. Thus, prenatal myelomeningocele diagnosis within the therapeutic window became a mandatory goal; therefore, research efforts on screening strategies were intensified, especially in the first trimester. In addition, different fetal surgery techniques were developed to improve neurological outcomes and reduce maternal risks. The objective of this review is to provide an update on the advances in prenatal screening and diagnosis during the first and second trimesters, and in open and fetoscopic fetal surgery for myelomeningocele.
Topics: Female; Fetoscopy; Humans; Meningomyelocele; Pregnancy; Prenatal Care; Prenatal Diagnosis
PubMed: 34033426
DOI: 10.5546/aap.2021.eng.e215 -
American Journal of Obstetrics and... Feb 2023As prenatal exome sequencing becomes integrated into clinical care, it is critical that providers caring for women with fetal anomalies recognize not only the benefits,... (Review)
Review
As prenatal exome sequencing becomes integrated into clinical care, it is critical that providers caring for women with fetal anomalies recognize not only the benefits, but also the challenges and considerations related to this technology. This overview of prenatal sequencing includes information about indications for sequencing, methods, diagnostic yield, clinical utility, variant interpretation, ethical considerations and dilemmas, practical considerations (ie, turnaround time and cost), pre- and posttest counseling points, and psychological impact of testing on families.
Topics: Pregnancy; Humans; Female; Ultrasonography, Prenatal; Exome; Genetic Counseling; Prenatal Care; Counseling; Fetus; Prenatal Diagnosis
PubMed: 36027950
DOI: 10.1016/j.ajog.2022.08.040 -
Journal of Medicine and Life 2019The last decade has seen incredible advances in the genetic era, in next-generation sequencing of cell-free DNA in the maternal plasma, detecting abnormal fetal... (Review)
Review
The last decade has seen incredible advances in the genetic era, in next-generation sequencing of cell-free DNA in the maternal plasma, detecting abnormal fetal chromosomes. Non-invasive prenatal testing (NIPT) has showed increased sensitivity and specificity for Down syndrome superior to any other screening test. Technical advances have made possible the detection of other conditions which does not necessarily mean clinical benefit for the patient. Private laboratories have added multiple conditions in the panel of NIPT, but some of these abnormalities are so rare, that their prevalence is not even clear. Data regarding clinical performance of extended NIPT is lacking. Implementation of such a test has to be carefully weighed, and not only the benefits but also the harm should be taken into account.
Topics: Counseling; Down Syndrome; Female; Fetus; Humans; Pregnancy; Prenatal Diagnosis; Trisomy; World Health Organization
PubMed: 31666820
DOI: 10.25122/jml-2019-0053 -
Ultrasound in Obstetrics & Gynecology :... Aug 2020
Topics: Adult; Biometry; Female; Fetal Development; Fetal Growth Retardation; Humans; Infant, Newborn; Infant, Small for Gestational Age; Obstetrics; Pregnancy; Prenatal Diagnosis
PubMed: 32738107
DOI: 10.1002/uog.22134 -
BMJ Open Jul 2019To assess international trends and patterns of prenatal diagnosis of critical congenital heart defects (CCHDs) and their relation to total and live birth CCHD prevalence...
OBJECTIVES
To assess international trends and patterns of prenatal diagnosis of critical congenital heart defects (CCHDs) and their relation to total and live birth CCHD prevalence and mortality.
SETTING
Fifteen birth defect surveillance programmes that participate in the International Clearinghouse for Birth Defects Surveillance and Research from 12 countries in Europe, North and South America and Asia.
PARTICIPANTS
Live births, stillbirths and elective terminations of pregnancy for fetal anomaly diagnosed with 1 of 12 selected CCHD, ascertained by the 15 programmes for delivery years 2000 to 2014.
RESULTS
18 243 CCHD cases were reported among 8 847 081 births. The median total prevalence was 19.1 per 10 000 births but varied threefold between programmes from 10.1 to 31.0 per 10 000. CCHD were prenatally detected for at least 50% of the cases in one-third of the programmes. However, prenatal detection varied from 13% in Slovak Republic to 87% in some areas in France. Prenatal detection was consistently high for hypoplastic left heart syndrome (64% overall) and was lowest for total anomalous pulmonary venous return (28% overall). Surveillance programmes in countries that do not legally permit terminations of pregnancy tended to have higher live birth prevalence of CCHD. Most programmes showed an increasing trend in prenatally diagnosed CCHD cases.
DISCUSSION AND CONCLUSIONS
Prenatal detection already accounts for 50% or more of CCHD detected in many programmes and is increasing. Local policies and access likely account for the wide variability of reported occurrence and prenatal diagnosis. Detection rates are high especially for CCHD that are more easily diagnosed on a standard obstetric four-chamber ultrasound or for fetuses that have extracardiac anomalies. These ongoing trends in prenatal diagnosis, potentially in combination with newborn pulse oximetry, are likely to modify the epidemiology and clinical outcomes of CCHD in the near future.
Topics: Asia; Europe; Female; Heart Defects, Congenital; Humans; Infant, Newborn; Male; North America; Pregnancy; Prenatal Diagnosis; Prevalence; Retrospective Studies; South America
PubMed: 31270117
DOI: 10.1136/bmjopen-2018-028139 -
Prenatal Diagnosis Dec 2022Fetal cerebral ventriculomegaly is a relatively common finding, observed during approximately 1% of obstetric ultrasounds. In the second and third trimester, mild... (Review)
Review
Fetal cerebral ventriculomegaly is a relatively common finding, observed during approximately 1% of obstetric ultrasounds. In the second and third trimester, mild (≥10 mm) and severe ventriculomegaly (≥15 mm) are defined according to the measurement of distal lateral ventricles that is included in the routine sonographic examination of central nervous system. A detailed neurosonography and anatomy ultrasound should be performed to detect other associated anomalies in the central nervous system and in other systems, respectively. Fetal MRI might be useful when neurosonography is unavailable or suboptimal. The risk of chromosomal and non-chromosomal genetic disorders associated with ventriculomegaly is high, therefore invasive genetic testing, including microarray, is recommended. Screening for prenatal infections, in particular cytomegalovirus and toxoplasmosis, should also be carried out at diagnosis. The prognosis is determined by the severity of ventriculomegaly and/or by the presence of co-existing abnormalities. Fetal ventriculoamniotic shunting in progressive isolated severe ventriculomegaly is an experimental procedure. After delivery, ventricular-peritoneal shunting or ventriculostomy are the two available options to treat hydrocephalus in specific conditions with similar long-term outcomes. A multidisciplinary fetal neurology team, including perinatologists, geneticists, pediatric neurologists, neuroradiologists and neurosurgeons, can provide parents with the most thorough prenatal counseling. This review outlines the latest evidence on diagnosis and management of pregnancies complicated by fetal cerebral ventriculomegaly.
Topics: Pregnancy; Child; Female; Humans; Prospective Studies; Hydrocephalus; Ultrasonography, Prenatal; Nervous System Malformations; Parents; Cerebral Ventricles; Prenatal Diagnosis
PubMed: 36371614
DOI: 10.1002/pd.6266 -
Taiwanese Journal of Obstetrics &... Mar 2022To investigate the phenotypes, biochemical features and genotypes for 244 pedigrees with methylmalonic aciduria (MMA) in China, and to perform the prenatal genetic...
OBJECTIVES
To investigate the phenotypes, biochemical features and genotypes for 244 pedigrees with methylmalonic aciduria (MMA) in China, and to perform the prenatal genetic diagnosis by chorionic villus for these pedigrees.
MATERIALS AND METHODS
Gene analyses were performed for 244 pedigrees. There are 130 pedigrees, chorionic villus sampling was performed on the pregnant women to conduct the prenatal diagnosis.
RESULTS
Among 244 patients, 168 (68.9%) cases were combined methylmalonic aciduria and homocystinuria, 76 (31.1%) cases were isolated methylmalonic aciduria. All the patients were diagnosed with MMA by their clinical manifestation, elevated blood propionylcarnitine, propionylcarnitine to acetylcarnitine ratio, and/or urine/blood methylmalonic acid with or without homocysteine. MMACHC, MMUT, SUCLG1 and LMBRD1 gene variants were found in 236 (96.7%) pedigrees included 6 probands with only one heterozygous variant out of 244 cases. For the 130 pedigrees who received a prenatal diagnosis, 22 fetuses were normal, 69 foetuses were carriers of heterozygous variants, and the remaining 39 foetuses harboured compound heterozygous variants or homozygous variants. The follow-up results were consistent with the prenatal diagnosis.
CONCLUSION
The present study indicates genetic heterogeneity in MMA patients. Genetic analysis is a convenient method for prenatal diagnosis that will aid in avoiding the delivery of MMA patients.
Topics: Amino Acid Metabolism, Inborn Errors; China; Female; Genotype; Humans; Nucleocytoplasmic Transport Proteins; Oxidoreductases; Pedigree; Pregnancy; Prenatal Diagnosis
PubMed: 35361390
DOI: 10.1016/j.tjog.2022.02.017 -
Archives of Gynecology and Obstetrics Apr 2022Screening for chromosomal disorders, especially for trisomy 21, has undergone a number of changes in the last 50 years. Today, cell-free DNA analysis (cfDNA) is the... (Review)
Review
Screening for chromosomal disorders, especially for trisomy 21, has undergone a number of changes in the last 50 years. Today, cell-free DNA analysis (cfDNA) is the gold standard in screening for trisomy 21. Despite the advantages that cfDNA offers in screening for common trisomies, it must be recognized that it does not address many other chromosomal disorders and any of the structural fetal anomalies. In the first trimester, the optimal approach is to combine an ultrasound assessment of the fetus, which includes an NT measurement, with cfDNA testing. If fetal structural defects are detected or if the NT thickness is increased, an amniocentesis or a CVS with at least chromosomal microarray should be offered.
Topics: Chromosome Aberrations; Female; Humans; Nuchal Translucency Measurement; Pregnancy; Pregnancy Trimester, First; Prenatal Diagnosis; Trisomy
PubMed: 35279726
DOI: 10.1007/s00404-022-06477-5 -
European Journal of Human Genetics :... Jan 2021Despite clear technical superiority of genome sequencing (GS) over other diagnostic methods such as exome sequencing (ES), few studies are available regarding the...
Despite clear technical superiority of genome sequencing (GS) over other diagnostic methods such as exome sequencing (ES), few studies are available regarding the advantages of its clinical application. We analyzed 1007 consecutive index cases for whom GS was performed in a diagnostic setting over a 2-year period. We reported pathogenic and likely pathogenic (P/LP) variants that explain the patients' phenotype in 212 of the 1007 cases (21.1%). In 245 additional cases (24.3%), a variant of unknown significance (VUS) related to the phenotype was reported. We especially investigated patients which had had ES with no genetic diagnosis (n = 358). For this group, GS diagnostic yield was 14.5% (52 patients with P/LP out of 358). GS should be especially indicated for ES-negative cases since up to 29.6% of them could benefit from GS testing (14.5% with P/LP, n = 52 and 15.1% with VUS, n = 54). Genetic diagnoses in most of the ES-negative/GS-positive cases were determined by technical superiority of GS, i.e., access to noncoding regions and more uniform coverage. Importantly, we reported 79 noncoding variants, of which, 41 variants were classified as P/LP. Interpretation of noncoding variants remains challenging, and in many cases, complementary methods based on direct enzyme assessment, biomarker testing and RNA analysis are needed for variant classification and diagnosis. We present the largest cohort of patients with GS performed in a clinical setting to date. The results of this study should direct the decision for GS as standard second-line, or even first-line stand-alone test.
Topics: Adolescent; Child; Child, Preschool; Female; Gene Frequency; Genetic Diseases, Inborn; Genetic Testing; Humans; Infant; Infant, Newborn; Male; Prenatal Diagnosis; Sensitivity and Specificity; Exome Sequencing
PubMed: 32860008
DOI: 10.1038/s41431-020-00713-9